Kmt5b-KO Mouse

KMT5B, also known as SUV4-20H1, is a lysine methyltransferase. It is involved in histone modification, regulating gene expression during brain development [7]. The genes it regulates are associated with nervous system development and function, including pathways like axon guidance signaling [1].

Pathogenic variants in KMT5B are linked to neurodevelopmental disorders such as global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788) [1,3,4,5,6,7,8]. KMT5B homozygous knockout mice are smaller than wild-type littermates, with relative macrocephaly, similar to the clinical feature in patients [1]. Kmt5b haploinsufficient mice show deficits in neonatal reflexes, sociability, and repetitive stress-induced grooming, along with differences in thermal pain sensing, depression, anxiety, fear, and extinction learning. There are also sexually dimorphic differences, mirroring the sex bias in ASD [9]. In addition, Kmt5b haploinsufficiency in mice results in a skeletal muscle developmental deficit, reducing muscle mass and body weight [2].

In conclusion, KMT5B is essential for normal neurodevelopment and muscle development. Mouse models, especially gene-knockout models, have been crucial in revealing its role in these processes and its association with neurodevelopmental disorders, highlighting the importance of this gene in understanding the underlying mechanisms of related diseases.